| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Active Psoriatic Arthritis |
|
| E.1.1.1 | Medical condition in easily understood language |
| Active Psoriatic Arthritis |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10037160 |
| E.1.2 | Term | Psoriatic arthritis |
| E.1.2 | System Organ Class | 100000004859 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
• To evaluate the differences in proportions of participants achieving composite 20% ACR20 clinical response after 16 weeks of treatment with VTX958 compared with placebo.
• To assess the safety and tolerability of VTX958 in participants with PsA. |
|
| E.2.2 | Secondary objectives of the trial |
| To compare the efficacy of VTX958 versus placebo on improvement of PsA following treatment for up to 16 weeks. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Men or women, aged 18 to 75 years, inclusive, at the time of consent.
2. Body mass index within the range of 18 to 40 kg/m2, inclusive, and total body weight > 50 kg (110 lb).
3. Capable of giving signed informed consent.
4. Diagnosed with PsA for ≥ 6 months before Screening, and who meet the CASPAR at Screening.
5. Must be negative for rheumatoid factor and anti-CCP antibodies.
6. Must have a documented history or active signs of at least one of the following at Screening:
a. At least 1 confirmed lesion of plaque psoriasis of at least 2 cm,
b. Nail changes attributed to psoriasis.
7. Active PsA as defined by ≥ 3 swollen joints (SJC66) and ≥ 3 tender joints (TJC68) at Screening and Day 1; these need not be the same joints at Screening and Day 1.
8. Demonstrated inadequate response to, loss of response to, or intolerance to at least one of the following therapies:
a. Conventional nonbiologic DMARDs (eg, methotrexate, leflunomide, sulfasalazine, or hydroxychloroquine), or apremilast,
b. NSAIDs,
c. Corticosteroids.
9. Participant either (i) did not have prior exposure to biologics (biologic-naïve) or (ii) have failed or been intolerant to 1 TNFi or 1 IL-17 inhibitor. Failure is defined as lack of response or loss of response with ≥ 12 weeks of therapy with an approved dose of a TNFi or IL-17 inhibitor, as judged by the investigator. Failure must have occurred ≥ 8 weeks prior to Day 1 for TNFi and ≥ 12 weeks prior to Day 1 for an IL-17 inhibitors.
10. Participants are permitted to receive the following medications if doses and frequency are stable for ≥ 2 weeks prior to Day 1 and they agree to continue using them at the same dosage during the study:
a. NSAIDs if dose is consistent with labeling recommendations for pain,
b. Acetaminophen (≤ 4 g/day)/paracetamol,
c. Oral corticosteroids (≤ 10 mg/day prednisone equivalent),
d. Concurrent topical therapy for plaque psoriasis.
11. If on a conventional nonbiologic DMARD (eg, methotrexate, sulfasalazine, hydroxychloroquine, leflunomide; excludes apremilast), participants can continue using 1 DMARD provided it has been used for ≥ 12 weeks prior to Day 1 with a stable dose and frequency for ≥ 4 weeks prior to Day 1, at the same dosage during the study.
12. Women must meet either (a) or (b) of the following criteria and men must meet criterion (c) to qualify for the study:
a. A woman who is not of childbearing potential must meet 1 of the following:
•i. Postmenopausal, defined as no menses for 12 months without an alternative medical cause, and an FSH test with a result ≥ 30 mIU/mL, confirming nonchildbearing potential.
•ii. Permanent sterilization procedure, such as hysterectomy, bilateral salpingectomy, or bilateral oophorectomy.
b. A nonpregnant woman of childbearing potential must agree to use a highly effective contraception method that can achieve a failure rate of less than 1% per year when used consistently and correctly. The highly effective contraception must be used through the duration of the study and for 30 days after the last dose of study product. The following are considered highly effective birth control methods:
•Combined (estrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation, which may be oral, intravaginal, or transdermal,
•Progesterone-only hormonal contraception associated with inhibition of ovulation, which may be oral, injected, or implanted,
•Intrauterine device,
•Intrauterine hormone-releasing system,
•Bilateral tubal occlusion,
•Vasectomized partner, provided that the partner is the sole sexual partner of the woman of childbearing potential study participant and the vasectomized partner has received medical assessment of the surgical success,
•Sexual abstinence (complete sexual abstinence, defined as refraining from heterosexual intercourse for the entire period of risk associated with study products). The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not acceptable.
c. A man with a pregnant or nonpregnant partner who is a woman of childbearing potential must agree to use condoms through the duration of the study and for 90 days after the last dose of study product.
d. Female participants must agree to not have egg retrieval from Day 1 until at least 30 days after the last dose of study product. Male participants must refrain from donating sperm from Day 1 until at least 90 days after the last dose of study product. |
|
| E.4 | Principal exclusion criteria |
1.Has non-plaque psoriasis at Screening or Day 1.
2.Has any disorder that, in the opinion of the investigator, would interfere with the study assessments.
3.Has a history or evidence of active infection and/or febrile illness ≤ 7 days prior to Day 1.
4.Has a history of serious infections requiring hospitalization and/or intravenous antibiotic ≤ 12 weeks prior to Day 1, or any infection requiring oral antibiotic ≤ 4 weeks prior to Day 1.
5.Has a history of chronic or recurrent infectious disease.
6.Has a history of infected prosthesis or has received antibiotics for a suspected infection of a joint prosthesis if that prosthesis has not been removed or replaced.
7.Has an active herpes simplex infection.
8.Has a known immune deficiency or is immunocompromised.
9.Has hepatitis B infection:
•Acute or chronic hepatitis B infection, or
•A positive result for HBV at Screening.
10.Has hepatitis C infection:
•Current hepatitis C infection, or
•A positive result for HCV at Screening.
11.Has current HIV infection or AIDS, or positive HIV antibody at Screening.
12.Has active latent TB infection at Screening. History of untreated or inadequately treated latent TB infection.
13.Has had previous exposure to VTX958 or any other TYK2 inhibitor in any study.
14.Has had prior treatment with ustekinumab, tildrakizumab, risankizumab, guselkumab, or cyclophosphamide.
15.Has had treatment with secukinumab, bimekizumab, and ixekizumab < 12 weeks prior to Day 1.
16.Has had treatment with any experimental therapy or new investigational agent ≤ 4 weeks or 5 half-lives prior to Day 1 or is currently enrolled in an investigational study.
17.Has had treatment with etanercept, adalimumab, infliximab, certolizumab, or golimumab (or other TNFi) < 8 weeks prior to Day 1.
18.Has had prior treatment with lymphocyte-depleting therapies, or agents that modulate B- or T-cells.
19.Has received any live or live-attenuated vaccine within 4 weeks prior to Day 1 or plans to receive a live or live-attenuated vaccine during the study and up to 4 weeks or 5 half-lives, whichever is longer, after the last dose of study drug.
20.Has had prior treatment with any approved or investigational JAK inhibitors.
21.Has received systemic psoriasis medications other than biologics and/or any systemic immunosuppressants therapy ≤ 4 weeks prior to Day 1.
22.Has received phototherapy ≤ 4 weeks prior to Day 1.
23.Has used topical medications/treatments that could affect psoriasis evaluation ≤ 2 weeks prior to Day 1.
24.Has used shampoos that contain corticosteroids, coal, tar, or vitamin D3 analogs ≤ 2 weeks prior to Day 1.
25.Has used any high potency opioid analgesic at average daily doses of > 30 mg/day of oral morphine or its equivalent or use of variable doses of any opiate analgesic ≤ 6 weeks prior to Day 1.
26.Is pregnant, lactating, or has a positive serum β-hCG measured during Screening.
27.Has had any major surgery ≤ 8 weeks prior to Day 1, or any planned surgery during the study.
28.Has any clinically significant medical condition in the opinion of the investigator, put the participant at undue risk or interfere with interpretation of study results.
29.Has unstable cardiovascular disease, defined as a recent clinical deterioration, or a cardiac hospitalization ≤ 3 months prior to Screening.
30.Has uncontrolled arterial hypertension.
31.Has Class III or IV congestive heart failure by NYHA criteria.
32.Has been hospitalized in the past 3 months for asthma, has ever required intubation for treatment of asthma, currently require oral corticosteroids for the treatment of asthma, or has required more than 1 short-term course of oral corticosteroids for asthma ≤ 6 months prior to Day 1.
33.Has a history of cancer or lymphoproliferative disease within 5 years prior to Day 1.
34.Has a known history of clinically significant drug or alcohol abuse in the last year prior to Screening.
35.Has any of the following laboratory values at Screening:
a. ALT or AST values ≥ 2.0 × ULN,
b. Hemoglobin < 9 g/dL,
c. Absolute WBC count < 3.0 × 10^9/L,
d. Absolute neutrophil count < 1.0 × 10^9/L,
e. Absolute lymphocyte count < 0.5 × 10^9/L,
f. Platelet count < 100 × 10^9/L,
g. Total bilirubin ≥ 1.5 × ULN,
h. Estimated glomerular filtration rate < 60 mL/min/1.73 m2 by the Chronic Kidney Disease Epidemiology Collaboration equation at Screening,
i. TSH outside the normal range deemed clinically significant by the investigator.
36.Has any other significant laboratory or procedure abnormalities that, in the opinion of the investigator, might place the participant at unacceptable risk for participation in this study.
37.Has history of any significant drug allergy or intolerance or allergy to any component of IMP.
38.Has donated > 50 mL of blood or plasma ≤ 4 weeks of Screening
or > 499 mL of blood or plasma ≤ 8 weeks prior to Screening
or intends to donate blood during the course of study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
-Proportion of participants achieving ACR20 response at Week 16.
-Incidence of TEAEs. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
-Week 16
-Throughout the whole duration of the study |
|
| E.5.2 | Secondary end point(s) |
1. Change from baseline in HAQ-DI at Week 16.
2. Proportion of participants achieving PASI75 response at Week 16 in participants with at least 3% BSA involvement at baseline.
3. Change from baseline in SF-36 PCS at Week 16.
4. Proportion of participants achieving ACR50 response at Week 16.
5. Proportion of participants achieving ACR70 response at Week 16. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Study consists of a 16-week Treatment Period plus an 36-week LTE Treatment Period |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 42 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| United States |
| Poland |
| Bulgaria |
| Spain |
| Czechia |
| Germany |
| Hungary |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
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